Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Hui Guo,Jiangtao Ma,Yanli Zhang,Yan Mao,Ziwei Hu,Ying Lin,Feng Yu,Wei Wang,Yaling Liu
An autoimmune condition known as systemic lupus erythematosus (SLE) is characterized by B cell hyperresponsiveness and persistent generation of pathogenic autoantibodies that cause damage to various organs and tissues. The treatments available today are either ineffective or have adverse effects. The dysregulation of B cell activation is crucial for the emergence of SLE. MiR-7 explicitly targeted PTEN mRNA in B cells. Treatment with antagomiR-7 reduced B cell hyperresponsiveness and prevented the onset of lupus. As a result, inhibiting miR-7 may be used therapeutically to treat SLE. We developed a SA (sialic acid)-poly (D, L-lactide-co-glycolide) (SA-PLGA) nano delivery system to deliver antagomiR-7 into splenic B cells since the stability and targeted delivery of miRNA remain significant challenges in vivo . Results show that SA-PLGA nanoparticles (SA-PLGA@antagomiR-7) loaded with antagomiR-7 display good biocompatibility and shield antagomiR-7 from degradation, extending the miRNA’s duration in circulation in vivo . Additionally, in MRL/Ipr lupus mice, SA-PLGA@antagomiR-7 is successfully delivered to the splenic B cells and preferentially enriched in the diseased spleen in MRL/Ipr lupus mice. The SA-PLGA@antagomiR-7 NPs therapy effectively decreases immunological abnormalities, normalizes splenic B cell subtypes, and suppresses B cell activation. The antagomiR-7 NPs exhibit excellent therapeutic efficiency and high biosafety collectively, which may result in a more effective treatment for SLE.
研究领域:
免疫学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 9
·3877
·
IF 13.3
Yueyang Li,Yu Zhai,Tianling Wang,Siya Wang,Yu Tian,Zhiqun Bian,Yang Zhang,Chao Zhang,Minghan Liu,Changqing Li
Rationale: Nucleus pulposus (NP) fibrosis is a contributing factor to intervertebral disc degeneration (IVDD), which lacks an effective treatment. This study focuses on elucidating the role and mechanisms of the TGF-β signaling repressor SKI in NP fibrosis and exploring its therapeutic potential. Methods: Single-cell RNA sequencing (scRNA-seq) was used to investigate fibrotic nucleus pulposus cell (NPC) subsets and assess TGF-β signaling activation. Two recombinant plasmids encoding single-chain variable fragments (scFvs) targeting the fibrotic NPC marker FAP and SKI mRNA were co-transfected into HEK-293T cells to yield functionalized exosomes (EX ski+scFv ). The addition of EX ski+scFv to a gelatin/oxidized sodium alginate hydrogel produced a pH-responsive exosome/hydrogel system named Gel@EX ski+scFv . The therapeutic effects and underlying mechanism of Gel@EX ski+scFv were evaluated by RNA sequencing, molecular docking and coimmunoprecipitation. Results: A fibrotic NPC subset was characterized by elevated FAP and diminished SKI expression, along with activation of the TGF-β signaling pathway. SKI overexpression reduced fibrosis in TGF-β-treated NPCs. EX ski+scFv successfully delivered SKI mRNA to FAP-expressing fibrotic NPCs. Gel@EX ski+scFv possessed good mechanical properties, degradability, injectability, and biocompatibility. Gel@EX ski+scFv effectively alleviated NP fibrosis and IVDD in rats. RNA sequencing, molecular docking and coimmunoprecipitation revealed that SKI could interact with FOXO3 to suppress the TGF-β signaling pathway. Conclusion: This study elucidates the mechanism by which SKI -mediated TGF-β signaling inhibition alleviates NP fibrosis. The development of the Gel@EX ski+scFv system for the targeted delivery of SKI mRNA offers a promising therapeutic strategy to alleviate NP fibrosis and IVDD in the future.
研究领域:
生物医学
·
分子生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lei huang,Siyuan Tang,Jiachen Guo,Yixing Tu,Sian Li,Xianchao Dai,Taihua Yang,Dong Zhao,Chao Wang
The development of tumor-retained and minimally invasive mRNA and photothermal therapies for superficial malignant tumors, such as breast cancer, remains a significant challenge. In this study, we present a novel tumor-retained lipid nanoparticle-microneedle (LNP-MN) patch for localized co-delivery of mRNA and the photothermal agent indocyanine green (ICG). By optimizing LNP formulations, ICG loading methodology, mRNA-to-ICG ratio, and MN matrix composition, we achieved a balanced platform ensuring high mRNA transfection efficiency and robust ICG photothermal performance. This LNP-MN platform enabled efficient intratumoral deposition, demonstrating a 15.6-fold increase in tumor accumulation compared to intravenous administration. For the first time, SARS-CoV-2 spike mRNA was combined with ICG-mediated photothermal therapy (PTT) within a single system for superficial tumor treatment. In a 4 T1 breast cancer model, this combinatorial strategy achieved significant tumor growth inhibition (75.1 %), enhanced CD8+ T-cell infiltration, and minimized systemic toxicity, outperforming monotherapies. This study pioneers the integration of PTT and mRNA-based tumor-labeling immunotherapy in a minimally invasive MN platform, offering a promising strategy for enhanced superficial cancer therapy.
研究领域:
纳米医学
·
癌症免疫治疗
·
药物递送系统
·
光热治疗
·
mRNA疫苗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
·
2020
·
IF 2.219
Xi Yuan,Yuxin Lin,Jingkai Qin,Yazhou Zhang,Guokun Yang,Ruijian Cai,Zongzhen Liao,Caiyun Sun,Wensheng Li
Red-spotted grouper ( Epinephelus akaara ) is one of the high economic value grouper species, however, the knowledge regarding its growth is limited. In this study, full-length cDNAs of growth hormone ( gh ) and its receptors ( ghr1 and ghr2 ) were cloned from the pituitary and liver of red-spotted grouper, respectively. Tissue distribution analysis showed that gh mRNA was predominantly expressed in the pituitary. ghr1 mRNA was highly expressed in the liver, muscle, fat and gonad, while ghr2 mRNA expression was ubiquitously high in the peripheral tissues. However, the mRNA expression of both ghr isoforms was relatively low in the central nervous system. Secretory recombinant grouper GH (rgGH) was expressed in yeast Pichia pastoris and verified. HEK293T cells transiently transfected with the GHR isoforms were used to elucidate the receptor-mediated signaling pathways related to growth regulation. rgGH activated rapid phosphorylation of Janus kinase 2, signal transducer and activator of transcription 5 (STAT5) and extracellular signal-regulated protein kinase 1/2 through GHR1, but only STAT5 was phosphorylated via GHR2. rgGH strongly activated STAT5 phosphorylation and significantly stimulated ghr1 , ghr2 and insulin-like growth factor ( igf1 , igf2 ) mRNA expression in primary cultured hepatocytes. Data showed that the recombinant protein rgGH played effects on igf1 / 2 mRNA expression via GHR-mediated signaling pathways. Our findings provide essential information about GH and GHRs characteristics in red-spotted grouper.
研究领域:
水产养殖
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Medicine
·
2022
·
IF 5.058
Lifang Ye,Yu Zuo,Fang Chen,Yuetong Xu,Puli Zhang,Hongxia Yang,Sang Lin,Qinglin Peng,Guochun Wang,Xiaoming Shu
Objective In the current study, we aimed to assess resistin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of dermatomyositis patients with interstitial lung disease (DM-ILD) and their correlation with disease activity. Methods We detected resistin mRNA levels in the PBMCs of 37 DM-ILD, 8 DM patients without ILD, and 19 healthy control (HC) subjects by performing quantitative reverse transcription real-time polymerase chain reaction analysis. Associations between resistin expression levels and major clinical manifestations, laboratory examinations, and disease activity were also analyzed. In addition, resistin expression in lung specimens from patients with DM-ILD was examined via immunohistochemistry and immunofluorescence. Results Resistin mRNA levels in PBMCs were significantly higher in DM-ILD than that in DM patients without ILD and HCs ( p = 0.043, 0.014, respectively). Among these DM-ILD patients, the resistin levels were significantly elevated in those with rapidly progressive ILD than in those with chronic ILD ( p = 0.012). The resistin mRNA levels in DM-ILD positively correlated with serum alanine aminotransferase (r = 0.476, p = 0.003), aspartate aminotransferase (r = 0.488, p = 0.002), lactate dehydrogenase (r = 0.397, p = 0.014), C-reactive protein (r = 0.423, p = 0.008), ferritin (r = 0.468, p = 0.003), carcinoembryonic antigen (r = 0.416, p = 0.011), carbohydrate antigen 125 (r = 0.332, p = 0.047), interleukin-18 (r = 0.600, p < 0.001), and lung visual analog scale values (r = 0.326, p = 0.048), but negatively correlated with the diffusing capacity of carbon monoxide (DLco)% (r = −0.447, p = 0.041). Immunohistochemical analysis of resistin showed its elevated expression in the macrophages, alveolar epithelial cells, and weak fibrotic lesions from patients with DM-ILD. Immunofluorescence staining confirmed CD68+ macrophages co-express resistin. Conclusions Resistin levels were increased in patients with DM-ILD and associated with disease activity and ILD severity. Therefore, resistin may participate in the pathogenesis of DM-ILD and may act as a useful biomarker.
研究领域:
风湿病学
·
呼吸病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yuanyuan Chai,Yunxia Xu,Ziyin Xia,Xin Huang,Luyong Zhang,Zhenzhou Jiang
Ethnopharmacological relevance Zhuanggu Guanjie Pill (ZGGJP), a modern Chinese medicine formula, is composed of 12 herbs and has been used to treat osteoporosis in China for almost 30 years. However, no in vivo study of the influences of ZGGJP on the cytochrome P450 (CYP) activities have been reported. Aim of the study The aim of this study was to evaluate the effects of ZGGJP on the activities and the mRNA expression of CYP enzymes (CYP1A2, CYP2B6 , CYP2C9 , CYP2C19 , CYP2D6 , CYP2E1 and CYP3A) and their corresponding nuclear receptor levels in rats. Materials and methods After 7 days oral treatment of ZGGJP at low- and high-dose, cocktail solution was given to rats. Blood samples were collected at series of time points. The plasma concentrations of probe drugs and their corresponding metabolites were determined by UPLC-MS/MS. The influence of ZGGJP on the activities of seven CYPs were evaluated the metabolic ratios (C max and AUC 0-t) for metabolites/probe drugs. In addition, the effects of ZGGJP on the mRNA expression of CYPs and their corresponding nuclear receptors in rat liver were evaluated by real-time PCR. Results ZGGJP showed significant inductive effects on CYP1A2 and CYP2B6 of both male and female rats. The influence of ZGGJP on CYP2C9 and CYP3A showed gender difference. ZGGJP could induce the activities of CYP2C9 and CYP3A in female rats, but have no influence on the activities in male rats. ZGGJP had no effects on CYP2D6, CYP2C19 and CYP2E1. The mRNA expression results of CYPs were in accordance with the pharmacokinetic results. The mRNA expression levels of constitutive androstane receptor (CAR) and vitamin D receptor (VDR) were increased significantly in female rats at high dosage, but no significant changes were observed in male rats. Conclusion ZGGJP had inductive effects on CYP1A2 and CYP2B6 in both male and female rats. The results showed that ZGGJP could induce the activities of CYP2C9 and CYP3A in female rats, but had no effect in male rats. This may suggest that the influence of ZGGJP on CYP2C9 and CYP3A exhibit gender difference. The inductive effects of ZGGJP on the activities of CYPs, exhibiting gender difference, may be regulated by CAR and VDR. Therefore, co-administration of ZGGJP with other drugs, especially using CYP2C9 and CYP3A substrates in females, may need dose adjustment to avoid herb-drug interaction.
研究领域:
民族药理学
·
药物代谢
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 28
·
IF 12.5
Desheng Cao,Junliang Zhu,Yang Guo,Yang Zhou,Jia Zeng,Yuanyuan Tu,Ziyin Zhao,Laiqing Xie,E Song,Manhui Zhu,Lichen Yin
As an important modality for choroidal neovascularization (CNV) treatment, intravitreal injection of vascular endothelial growth factor A (VEGFA) inhibitors suffers from undesired response rate, low patient compliance, and ocular damage. Here, dynamically covalent lipid nanoparticles (LNPs) were engineered to mediate VEGFA gene editing and CNV treatment by codelivering Cas9 mRNA (mCas9) and single guide RNA (sgRNA) targeting VEGFA (sgVEGFA). A library of lipidoids bearing iminoboronate ester linkage was developed via facile “one-pot” synthesis, and the top-performing lipidoid-A 4 B 3 C 7 was formulated into LNP-A 4 B 3 C 7 with the highest mRNA transfection efficiency. Inside the diseased retinal pigment epithelial cells, LNPs were dissociated upon H 2 O 2 -triggered lipidoid degradation, facilitating mRNA/sgRNA release to potentiate the gene editing efficiency. In laser-induced CNV mice, mCas9/sgVEGFA@LNP-A 4 B 3 C 7 after single intravitreal injection led to pronounced VEGFA disruption and CNV area reduction, outperforming the clinical anti-VEGF drug in eliciting sustained therapeutic effect. This study establishes a robust nonviral platform for mRNA delivery and genome editing and renders a promising strategy for CNV treatment.
研究领域:
生物医学工程
·
基因治疗
·
眼科
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Guisong Shan,Wanrong Wang,Xueqian Li,Zhaoxing Zhai,Mengyu Liu,Rui Peng,Qiuting Sun,Huiru Zhang,Tao Guo,Xiaoyan He
Epithelial–mesenchymal transition (EMT) is a key driver of chemoresistance and poor clinical outcomes in cancer. Strategies to reverse EMT-mediated drug resistance and to dynamically monitor treatment response are critical for improving therapeutic efficacy. Previous studies have implicated METTL3-regulated N 6 -methyladenosine (m 6 A) methylation in promoting EMT and tumor progression,highlighting its potential as a therapeutic target. Here, we develop a glutathione-responsive biomimetic nanomedicine (termed ACVS) that encapsulates METTL3 inhibitors within tumor-targeting cell membrane vesicles for controlled drug release. ACVS effectively reverse EMT phenotypes in vitro in transforming growth factor-β (TGF-β)-induced EMT cell models and restory chemosensitivity to standard therapeutics. In vivo validation in tumor-bearing mice and patient-derived circulating tumor cells (CTCs) further demonstrate that METTL3 inhibition enhance tumor suppression when combine with chemotherapy. To dynamically assess the relationship between EMT and chemoresistance, we implement single-cell resolution in situ mRNA profiling, which revealed spatial heterogeneity in EMT marker expression correlated with drug response. These findings propose a combinatorial strategy to overcome chemoresistance through METTL3-targeted modulation of EMT, while providing a methodological framework for real-time treatment monitoring in personalized oncology.
研究领域:
癌症生物学
·
纳米医学
·
表观遗传学
·
药理学
·
分子生物学
·
精准医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Zhang Min,Zhang Bin,Liu Chengli,Preußner Marco,Ayachit Megha,Li Weiming,Huang Yafei,Liu Deyi,He Quanwei,Emmerichs Ann-Kathrin,Meinke Stefan,Chen Shu,Wang Lin,Zheng Liduan,Li Qiubai,Huang Qin,Haltenhof Tom,Gao Ruoxi,Qin Xianan,Cheng Aifang,Wei Tianzi,Yu Li,Schubert Mario,Gao Xin,Li Mingchang,Heyd Florian
Mammals tightly regulate their core body temperature, yet how cells sense and respond to small temperature changes remains incompletely understood. Here, we discover RNA G-quadruplexes (rG4s) as key thermosensors enriched near splice sites of cold-repressed exons. These thermosensing RNA structures, when stabilized, mask splice sites, reducing exon inclusion. Specifically, rG4s near splice sites of a cold-repressed poison exon in the neuroprotective RBM3 are stabilized at low temperatures, leading to exon exclusion. This enables evasion of nonsense-mediated decay, increasing RBM3 expression at cold. Importantly, stabilizing rG4 through increasing intracellular potassium with an FDA-approved potassium channel blocker, mimics the hypothermic effect on alternative splicing, thereby increasing RBM3 expression, leading to RBM3-dependent neuroprotection in a mouse model of subarachnoid hemorrhage. Our findings unveil a mechanism how mammalian RNAs directly sense temperature and potassium perturbations, integrating them into gene expression programs. This opens new avenues for treating diseases arising from splicing defects and disorders benefiting from therapeutic hypothermia, especially hemorrhagic stroke.
研究领域:
分子生物学
·
神经科学
·
RNA生物学
·
温度生物学
·
基因表达调控
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Yun Zhao,Ruomeng Li,Junlin Sun,Zhiqiao Zou,Fuan Wang,Xiaoqing Liu
High mortality and rapid development of metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery, radiation therapy, and chemotherapy, show less effectiveness in curbing the metastatic spread of cancer cells and the formation of metastases. A therapeutic platform, targeting the early stage of metastasis cascade, could effectively prevent metastasis dissemination. Herein, Fe/Mn-based metal–organic frameworks (FMM) were constructed for the delivery of a specific DNAzyme with high catalytic cleavage activity on the metastasis-involved Twist mRNA, thus efficiently inhibiting the invasion of cancer cells through DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic therapy is achieved from the self-supplied DNAzyme cofactors and efficient glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist DNAzyme with efficient gene therapy. Consequently, the effective elimination of tumors and the blockage of metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile theranostic agents to combat metastatic tumors.
研究领域:
癌症研究
·
纳米医学
·
基因治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR & MOLECULAR BIOLOGY LETTERS
·
2023
·Vol. 28
·期 1
·1-24
·
IF 8.3
Lei Ming,Lin Hui,Shi Deyao,Hong Pan,Song Hui,Herman Bomansaan,Liao Zhiwei,Yang Cao
Background Intervertebral disc degeneration (IVDD) is the major cause of low-back pain. Histone deacetylase 9 (HDAC9) was dramatically decreased in the degenerative nucleus pulposus (NP) samples of patients with intervertebral disc degeneration (IVDD) according to bioinformatics analysis of Gene Expression Omnibus (GEO) GSE56081 dataset. This study aims to investigate the role of HDAC9 in IVDD progression.Methods The contribution of HDAC9 to the progression of IVDD was assessed using HDAC9 knockout (HDAC9KO) mice and NP-targeted HDAC9-overexpressing mice by IVD injection of adenovirus-mediated HDAC9 under a Col2a1 promoter. Magnetic resonance imaging (MRI) and histological analysis were used to examine the degeneration of IVD. NP cells were isolated from mice to investigate the effects of HDAC9 on apoptosis and viability. mRNA-seq and coimmunoprecipitation/mass spectrometry (co-IP/MS) analysis were used to analyze the HDAC9-regulated factors in the primary cultured NP cells.Results HDAC9 was statistically decreased in the NP tissues in aged mice. HDAC9KO mice spontaneously developed age-related IVDD compared with wild-type (HDAC9WT) mice. In addition, overexpression of HDAC9 in NP cells alleviated IVDD symptoms in a surgically-induced IVDD mouse model. In an in vitro assay, knockdown of HDAC9 inhibited cell viability and promoted cell apoptosis of NP cells, and HDAC9 overexpression had the opposite effects in NP cells isolated from HDAC9KO mice. Results of mRNA-seq and co-IP/MS analysis revealed the possible proteins and signaling pathways regulated by HDAC9 in NP cells. RUNX family transcription factor 3 (RUNX3) was screened out for further study, and RUNX3 was found to be deacetylated and stabilized by HDAC9. Knockdown of RUNX3 restored the effects of HDAC9 silencing on NP cells by inhibiting apoptosis and increasing viability.Conclusion Our results suggest that HDAC9 plays an important role in the development and progression of IVDD. It might be required to protect NP cells against the loss of cell viability and apoptosis by inhibiting RUNX3 acetylation and expression during IVDD. Together, our findings suggest that HDAC9 may be a potential therapeutic target in IVDD.Graphical Abstract
研究领域:
骨科
·
分子生物学
·
治疗学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2026
·
IF 6.7
Miao He,Jinhua Chen,MuRilege Chao,Feifan Yin,Han Pan,Qiufeng Wang,Wenting Cheng,Zhongyun Wang,Yang Xiang
mRNA vaccines, as a new form of vaccine, are gradually revealing their potential in the field of tumor treatment. With the development of mRNA vaccines, monitoring their levels has become particularly important. In this work, a novel and innovative strategy was proposed for the first time, which directly used the target as crRNA and simultaneously triggered an entropy-driven split Cas12a system for triple signal amplification for the high-sensitivity detection of mRNA vaccines. This study broke the traditional full-length crRNA and innovatively designed a split crRNA structure, directly using the target mRNA as the variable sequence of the crRNA. This design avoided the need for additional introduction of variable sequences, thereby eliminating nonspecific signal leakage and multicomponent interference from the source. At the same time, the target molecule served as the initiating chain for the EDC reaction, allowing the split Cas12a system to be coupled with the entire entropy-driven reaction process, achieving efficient collaboration and triple signal amplification and significantly improving the detection sensitivity and specificity. Moreover, the entire detection process required only one reaction step, which was simple, fast, and efficient. The aim was to provide strategies for screening and pharmacokinetic studies of mRNA vaccines.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）